title: Porphyromonas gingivalis lipopolysaccharide activates canonical Wnt/β-catenin and p38 MAPK signalling in stem cells from the apical papilla.
abstract: As dental precursor cells, stem cells from the apical papilla (SCAP) are capable of forming roots and undergoing apexogenesis, which are impaired upon exposure to bacterial infection. Porphyromonas gingivalis is a common Gram-negative bacterium that is involved in pulpal and periapical infection. The purpose of this study was to investigate the effects of P. gingivalis lipopolysaccharide (LPS) on the Wnt/β-catenin and p38 mitogen-activated protein kinase (MAPK) signalling pathways in SCAP. As indicated by the IL-1β and TNF-α mRNA levels, P. gingivalis LPS induced the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, activation of the p38 MAPK and Wnt/β-catenin pathways was confirmed by the augmentation of phospho-p38 and β-catenin protein expression and increased expression of c-myc and cyclin D1 mRNA. Despite no significant increase in β-catenin mRNA expression, increased phosphorylation of glycogen synthase kinase (GSK)-3β suggested that GSK-3β was responsible for the accumulation of β-catenin in the cytoplasm and translocation to the nucleus. Previous studies have shown that GSK-3β plays a critical role in crosstalk between the Wnt/β-catenin and p38 MAPK pathways. In the present study, we showed that the level of p38 phosphorylation decreased upon pretreatment with a p38 MAPK inhibitor for 1 h before stimulating SCAP with 10 μg/ml P. gingivalis LPS. However, the levels of GSK-3β and β-catenin phosphorylation in the cytoplasm and nucleus were not significantly altered. Our results suggest that the p38 MAPK and canonical Wnt/β-catenin signalling pathways are activated by P. gingivalis LPS in SCAP, but we have no evidence that p38 MAPK is upstream of GSK-3β in the Wnt/β-catenin signalling pathway.
authors.affiliation: Department of Endodontics and Operative Dentistry, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, No. 639, Zhizaoju Road, Shanghai, 200011, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Jiewen
authors.initials: J
authors.lastname: Dai
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Shensheng
authors.initials: S
authors.lastname: Gu
authors.forename: Lan
authors.initials: L
authors.lastname: Cheng
authors.forename: Jingping
authors.initials: J
authors.lastname: Liang
mesh_terms: D000293:Adolescent; D000328:Adult; D056624:Apexification; D019938:Cyclin D1 / Q000235:genetics; D003771:Dental Papilla / Q000166:cytology / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013234:Stem Cells; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3